Commentary: More Bad News On Antidepressants And Pregnancy

By Adam Urato, M.D.
Guest Contributor

Imagine for a moment that a virus started affecting about 5% of all pregnant women — 200,000 U.S. pregnancies per year. Imagine that it caused significant pregnancy complications above and beyond the baseline rate. More than 10% of those infected with the virus would miscarry; up to 20% or more would have preterm birth, and 30% of newborns would show effects of the exposure in the days after birth — sometimes severe, with seizures and trouble breathing. If this were to occur it would be considered a public health emergency and a tremendous effort would be put forth to address it. Yet this epidemic is happening and, in many ways, it is going unrecognized. Pregnant women and the public are unaware. It is the epidemic of antidepressant drug exposure during pregnancy.

Dr. Adam Urato, a maternal-fetal medical specialist, thinks women aren't getting the full story on antidepressants during pregnancy

Two articles came out last week showing that antidepressant use by pregnant women is associated with preterm birth. One of them also showed increased rates of neonatal seizures in newborns who were exposed to antidepressants in utero.

These articles join a large and growing body of literature that clearly demonstrates risks when pregnant women use antidepressants. These risks are all the more concerning given that there is no evidence of improvement of pregnancy outcomes with the use of antidepressants by pregnant women. There is an important question to ask: Are we exposing millions of pregnant women and their babies to a class of drugs that are causing significantly more harm than good?

Dangers Abound
Current research suggests that antidepressant use (typically the SSRIs) by pregnant women is associated with increased risks of miscarriage , birth defects, preterm birth, preterm premature rupture of membranes, preeclampsia, and decreased fetal growth.

After birth, newborns who were exposed to antidepressants in utero have increased rates of what is called the newborn behavioral syndrome which can consist of a variety of symptoms including tremors, agitation, excessive crying, respiratory difficulties, and seizures. Exposed newborns also have been shown to have changes in heart conduction (i.e, the prolonged QT syndrome) and a potentially fatal condition called Persistent Pulmonary Hypertension of the Newborn (PPHN) in which the arteries to the baby’s lungs are constricted leading to trouble breathing or, in severe cases, death.

Many of these risks are not rare. Rates of miscarriage in women taking antidepressants are estimated at greater than 10%. In some studies rates of preterm birth in the antidepressant exposed groups have been greater than 20%. Ten percent of babies exposed to SSRIs in utero will show the prolonged QT syndrome on their EKG . And up to 30% of exposed babies will develop the newborn behavioral syndrome.

Long Term Effects?
What is particularly concerning in this area is the issue of possible long term effects on the developing brains of exposed babies. Developing embryos and fetuses are loaded with serotonin receptors and the serotonergic system plays a crucial role in fetal development. What happens to human development of the brain and behavior when we alter this system? We simply have no idea and we are currently witnessing what amounts to a large uncontrolled experiment on human development.

The current research data is not reassuring. Animal data clearly shows that fetal exposure to antidepressants can lead to changes in the development of the brain and changes in behavior. Studies are available that demonstrate effects on the branching of neurons–the basic cell in the nervous system . Human studies have shown that children who were exposed to antidepressant in utero have changes in motor development and behavior. Last July (2011) researchers at Kaiser in California showed a doubling of the risk of autism with prenatal exposure to antidepressants. And this doesn’t appear to be a “chance” finding. For decades serotonin has been implicated in the etiology of autism .

Pregnant And Depressed

Many of these risks might be tolerable if there was evidence of pregnancy benefit with the use of antidepressants by pregnant women. “After all,” you might think, “cancer drugs have risks too but we use them because they cure cancer.” But, sadly, there is no evidence of obstetrical benefit with the use of these drugs by pregnant women. In study after study the group of women on the antidepressants have worse pregnancy outcomes, not better. For example, they have more miscarriages, more preterm birth, and more neonatal complications.

For years, the key opinion leaders in this area (most of whom are paid sizeable amounts by the drug industry) have been pitching the idea that pregnant women, by taking antidepressants, will improve their mood and that this will lead to better pregnancy outcomes. The conventional wisdom has been that depression is like diabetes and depressed pregnant women need to stay on their antidepressants just like pregnant diabetics need to take their insulin. And this counseling gets repeated on a daily basis in doctors’ offices around the globe and in news reports on this topic. The problem is that it just isn’t true: pregnancy outcomes do get better when diabetics take their insulin but this isn’t true with antidepressants. We had all hoped that the pregnancies of depressed women could be helped with drugs, but the scientific literature does not support the idea that antidepressant use in pregnancy improves outcomes. In fact, it’s just the opposite. When you take a group of depressed pregnant women and compare them to depressed pregnant women taking antidepressants, it’s the group that is taking the antidepressants that has the increased rates of pregnancy complications.

What’s A Woman To Do?

So what should we tell pregnant women and women of childbearing age who are taking these drugs? As a Maternal-Fetal Medicine consultant, I deal with this issue regularly. And for me the key is transparency and properly informing the patients and the public. Who can argue with giving pregnant women full information about a drug they are taking? And the truth is that full information in this area means telling women that antidepressant use during pregnancy has been associated, in study after study, with pregnancy complications and no evidence of better pregnancy results.

I frequently give lectures on this topic and am asked “What about the woman with severe depression who is suicidal when she comes off her antidepressant?” To me, it sounds like she should stay on the medication. But, let’s be clear, the vast majority of women on these drugs have mild to moderate depression. Furthermore, my main point on this is not that we should be telling anyone what to do. Psychotropic medication use during pregnancy is a personal choice and these women need care and support. But what they also need is accurate, correct, and complete information so they can make an informed decision; that is not what is currently happening.

We are currently seeing what amounts to an epidemic of antidepressant drug exposure during pregnancy and there is a pervasive lack of public information and understanding on this topic. Pregnant women need accurate information about drugs they take. I am surprised on a regular basis by my colleagues in obstetrics and psychiatry who are simply unaware of the large body of scientific studies clearly showing antidepressants to be associated with pregnancy complications. What pregnant patients choose to do with this information is up to them, but patients and the broader public deserve to be told the truth about the risks of antidepressant use during pregnancy.

Adam C. Urato, MD is a maternal-fetal medicine physician at Tufts Medical Center, Assistant Professor of Obstetrics & Gynecology at Tufts University School of Medicine and Chairman, Department of Obstetrics & Gynecology, MetroWest Medical Center in Framingham

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  • Marcia G.

    I suffered such bad ante natal depression
    that once I knew my child was viable outside the womb I was trying to
    figure out how I could get the police to shoot me in the head whilst
    having an ambulance there to cut my daughter out and save her. That’s
    how distorted my thinking became. And I don’t live in the States, we
    have public health care here, thank god- I had an awesome midwife and
    had access to really good care- they even had a room ready for me and my
    child at the mother/baby unit if I experienced post natal depression.
    Until
    you have gone through something that bad then I really don’t think you
    have any right to dismiss it as “feeling blue” or harangue people who
    might look at medication to help manage the symptoms. Wondering if your
    neighbours hose is long enough to use so you could gas yourself in your
    car, believing that killing yourself whilst saving your unborn child is
    the best, most loving thing you could do for that child… it is a very
    dark place to be and I think dialogue and education, not judgment, is
    what’s needed.

    http://www.haineonlinetari.com/

  • becca

    also on the issue of unbiased evidence: it is a well know fact that pharmaceutical companies pay large fees to the “researchers” who conduct their drug trials with an outcome that is favorable to their shareholders.that is not objective science.

  • becca

    speaking of unbiased, evidence based fact: legal documents of corporations such as pharmaceutical corporations clearly state that the primary legal obligation of these entities is to the share holders. If you think patient care is the first priority of these corporations you should gain a better understanding of the role of profits in these organizations.

  • Becca

    if you think there is no risk to the fetus–stay tuned to the money awards from the lawsuits in process. It will be millions–just a drop in the bucket to Big Pharma.

  • Becca

    you know what is really scary–for some of us it is not possible to stop taking the SSRI. If you only get your info from the drug manufacturers, you will think we are the minority of SSRI users. go online–there you will find the ocean of people suffering the SSRI withdrawal.Go to “quit Paxil,” or Zoloft or Effexor. I can see why Drs. and FDA would go along with the drug maker’s snow job at this point–the guilt of have having gotten milions of pole hooked on a drug that stops working but then is hell to detox. The suicide black box warning, finally admitting to a “Discontinuation syndrome”: all of these and other SSRI warnings were fought tooth and nail by big Pharma.They still claim there is no dependence created by these meds with their euphemistic “discontinuation syndrome” because heaven forbid that their cash cow should be associated with drug addictionterms, but they are as addictive as heroin and for many the withdrawal is as bad or worse–the brain zaps and spinning head to the point of extreme nausea are just the start. Let’s say, you’re one of the millions on Zoloft or Paxil and now you’re pregnant. so you know you have to get off this drug that puts your fetus at risk. Good luck! Luck is all you have because most doctors still do not credit the severity of the withdrawal. The only info is online. And even there the only advice is take supplements I finally talked to a drug rehab nurse who has been doing rehab for 30 years. She said “zoloft withdrawal is very similar to a benzo withdrawal” (which as some of you may know is considered one of the worst withdrawals) How would you feel if you were pregnant and knew your use of SSRI could lead to severe deformity of fetus and then you tried to quit the SSRI and couldn’t? I can understand the med. community denial of SSRI addiction–such guilt for hooking all these people who trusted you.The least you could do is research a withdrawal protocol but then you would have to admit there are severe withdrawal symptoms. (ANother fact that is little known is that SSRIs work in the brain like LSD)

  • Guest

    Not enough detail. What kinds of SSRIs were used in the studies?  How much were the doses?  Not helpful.

  • DrkPhnx

    This is an interesting article.  In my clinic I see children whose mothers often blame themselves for their child’s neurologic disease.  This natural guilt only adds to the difficulty of caring for their disabled child.  To be honest, I don’t think I’ve ever met a woman in whose case I could say, yes, this problem is definitely because of something you did (including medications taken).  Obviously, it is important to raise concerns about these drugs if they are scientifically valid (i.e. does the correlation mean causation), and to ensure that women should be well-informed.  But the doctor who has this discussion with a woman who must make the difficult decision about whether to stop taking her SSRI (I am assuming this is the class of drugs to which you refer) during pregnancy must understand *all* the implications of the discussion, including the implications of saying, “here are all the terrible things that can happen.  I am not going to tell you what to do, you should make your own choice.”  Where does that leave the woman, then?  No one wants to harm her baby.  We are socialized to believe that when pregnant we must strive to be some type of perfect vessel, and any misstep could cause the child lifelong problems.  The logical choice is, of course, to stop the medication.  But, it is unfair to place the burden of this decision on the shoulders of the pregnant woman.  If as her obstetrician you cannot guide her further, then she needs guidance from her psychiatrist (if she has one).  Is it safe for her to stop the medication?   There are risks besides suicide that come from untreated or improperly treated depression, ranging from poor eating, to disturbed sleep, to greater likelihood of substance abuse.  A mother who feels hopeless and miserable, or is more prone to post-partum depression, can’t be a ‘good outcome’ for her child. Of course, any woman who takes medication for a mental illness should be seeing someone who knows about the issues that arise with treatment during pregnancy.  The problem is that most people are prescribed these drugs by their primary care doctors.  Most people do not have therapists, when it seems that for mild depression therapy may be more effective than medication. I’m sure you know all of this.  I think the grey area is for the women in the “moderate depression” range, who probably do need treatment … but after being told what could happen, will be made to feel that it is their fault if there is anything wrong with the baby.  I think if you are going to have this conversation with women and leave “the ball in their court,” then you must also provide them with resources of therapists and psychiatrists who will see them promptly if they don’t have their own (covered by their insurance, taking new patients, of course).  Otherwise, you are putting some women in an extremely difficult position, one that could lead to lifelong guilt that may not be warranted, or to unnecessary personal suffering during the pregnancy. 

    P.S. ( As someone who has struggled for many years with episodic depression and sampled much of the pharmacopeia along with continuous talk therapy, which enables me to function fairly highly, I can tell you that “moderate depression” is not like having a cold, and pregnant women who have this *must* be given some other options if they choose to go off their SSRI’s.  It doesn’t just go from “a little depressed” to “suicidal.”  There are gradations of misery that should be acknowledged, and you are right that we must care for and support these women as they make this decision.  I have a jaundiced view of such a goal, though, because I think the therapists and psychiatrists that our patients need are just not out there.  I don’t know about you, but until my patients are having a crisis, I cannot get them help in a timely fashion no matter what I do.  That is why the implications of your article were a bit concerning to me, but I am not sure there is an easy solution either.)   

  • Rebecca

    I’m surprised to read no mention of specific antidepressants in this article. Would Dr. Urato like to follow up with further information on which specific drugs are the culprit of these particular complications. It is irresponsible to write an article on antidepressant use without distinguishing between different medications with vastly different components and effects on the body. Many severely depressed patients may be tempted to throw away their meds, when in fact they are on antidepressants which are less risky than those that have been implicated in these studies.

    • Rachel Zimmerman

      Another response from Dr. Urato:

      Rebecca raises a good issue regarding the fact that “antidepressants” is a general term and that there are different classes of antidepressants and different drugs within each class.   In most of the studies on this issue, most of the women were taking the selective serotonin reuptake inhibitors (SSRIs).  My comments about the risks of miscarriage, preterm birth, newborn withdrawal syndrome, etc focused predominantly on this class of antidepressants because that is the group for which we have the most data. Based on her post, though, I would ask her if in her reading of the literature there is an antidepressant drug  or class that she feels shows consistently reassuring data with regard to its use in pregnant women.

  • http://profile.yahoo.com/Q4QKYFTJ3CDDOP7LCR4KMLAOBE Deborah

    Too bad there isn’t more awareness of the therapeutic uses of tryptophan and 5-HTP (a serotonin precursor that the body makes from tryptophan) in treating depression. Prozac was originally marketed to psychiatrists in the 1980s as an aid to tryptophan – it would make the tryptophan’s effect last longer. One (suspiciously timed) bad batch of tryptophan in the early 1990s prompted the removal of tryptophan from the market, clinching SSRIs’ foothold. Surely a naturally occurring amino acid is highly preferable to an SSRI and should be the first line of treatment for everyone with depression, but particularly for women of childbearing age.

  • Sharon Haight-Carter

    As a women’s mental health advocate & clinician I’m shocked to see this doctor’s viewpoint that contrasts so sharply a large amount of data that shows untreated depression in pregnancy grave effects. Many psychiatrists refuse to treat depressed pregnant women and this leads to not only suicide, infanticide but also pre-term delivery, low birth weight, substance abuse, poor attachment & long term developmental problems in the child.
    Sharon Haight-Carter, PMHNP

    • Rachel Zimmerman

      I asked Dr. Urato to respond to Sharon Haight-Carter and here’s what he wrote:

       Sharon’s desire to provide proper care and counseling for depressed pregnant women is admirable and I share that desire.  What the studies actually show, however, is that antidepressant treatment during pregnancy is associated with increased rates of pregnancy complications (e.g. miscarriage, preterm birth, newborn behavioral syndrome).  She suggests in her comment that treatment of these depressed pregnant women will lead to fewer problems (for example, less preterm birth) but this is not what the evidence shows.  Study after study shows that when we take 2 groups of depressed pregnant women and one group is being treated with antidepressant medication, it is the treated group that has the increased rates of pregnancy complications.  Everyone has hoped, as Sharon does, that such treatment in these studies would lead to improved outcomes, but that just is not what the actual data shows.  The antidepressant-treated pregnancies are consistently faring worse.

      • Concerned Reader

        Again, he doesn’t specify which anti-depressants. The blanket way he discusses this is problematic. MGH’s Center for Women’s Health supports what Sharon Haight-Carter above says. I appreciate that WBUR is trying to give a “balanced” presentation, but he is not a specialist in mental health, and I find it irresponsible and harmful that he presents this issue as if it were more clear cut than it really is.

        MGH’s Center for Women has a really great run down of the evidence, pros and cons.
        http://www.womensmentalhealth.org/specialty-clinics/psychiatric-disorders-during-pregnancy/

        • Rachel Zimmerman

          Here’s Dr. Urato’s response to this comment:

          Concerned Reader calls the approach in my post “irresponsible and harmful” but all the piece is calling attention to is that the actual data on antidepressant use during pregnancy is very concerning.  Study after study shows complications with the use of these drugs in pregnancy.  Possible long-term developmental and behavioral issues in the exposed children are not proven but animal data (and several human studies) raise real concerns.  It would be irresponsible and harmful not to provide this information to patients and the public.Concerned Reader directs us to the MGH womensmentalhealth.org site for a balanced review of the evidence.  MGH is an excellent institution and I am proud to have trained there; however, I do not agree with the recommendation of this website.  Many of the staff members for the web site, including the director, associate director, director of research, and the director of clinical services are paid by the drug companies  http://www.womensmentalhealth.org/wp-content/uploads/2008/02/Faculty-Disclosures-updated-October-2011.pdf.  The site itself is also funded by a large number of drug companies.  The site discloses the following:  “The Center for Women’s Mental Health has received funding from the following sources over thepast 24 months:  Astra-Zeneca Pharmaceuticals; Bayer HealthCare Pharmaceuticals; Bristol-Myers Squibb; Eli Lilly &Company; Forest Laboratories, Inc.; GlaxoSmithKline; National Institute on Aging; National Institutes of Health; National Institute of Mental Health; Ortho-McNeil Janssen; Pfizer Inc.” For people looking for information on antidepressants and pregnancy that is not tainted by drug company dollars, I cannot recommend this website.  I encourage patients and the public to seek information on this area that is not tainted by the bias, or the suggestion of bias, that comes with drug industry funding.

          • Sally Guy

            As a psychiatric CNS I am often faced with helping women decide whether or not to stay on their antidepressants during pregnancy. Where can I send these women for unbiased, evidence-based research data if not http://www.womensmentalhealth.org? There is an organization in Toronto (motherisk.org) which has a clinical research and teaching program at the Hospital for Sick Children. They’ve been gathering data for 25 years which seems to support the findings of the MGH Women’s Mental Health Center. Gail Robinson MD, DPsych, director of the Women’s Mental Health Program at University Health Network in Toronto gave a talk at the 16th Annual Psychopharmacology Conference in November 2011 in which she said that the reports of risks are often overblown. Many of the research studies are quite small and don’t control for other risk factors such as age of mother, drug or alcohol abuse, etc. Furthermore, she said, when you really look closely at the data, the prematurity may be only a week, the lower birth weight is only 24 – 32 grams so these aren’t really as serious as they sound. She stresses the importance of reading the reports carefully; not just reading the abstracts. Where can I send my patients to get reliable, unbiased information about the risks of SSRIs during pregnancy?

          • invested reader

            I appreciate Dr. Urato’s willingness to respond to these comments.  It is very helpful to read the dialogue.  Dr. Urato, might you respond to this last question about where you would send patients to get reliable, unbiased information?  Your call to “encourage patients and the public to seek information on this area
            that is not tainted by the bias, or the suggestion of bias, that comes
            with drug industry funding” is challenging due to it’s lack of specificity.  I am a well-educated woman but find evaluating sources of medical information extremely difficult. 

          • Rachel Zimmerman

            Dr. Urato responds:

            Invested Reader wants to know where patients can get reliable, unbiased information on this topic.  This is a real challenge.  So many of the experts or “key opinion leaders” are paid by the antidepressant makers and much of the research in this area is also sponsored by the drug companies.  Many of the organizations or groups that focus on depression and pregnancy are also actively funded by industry.  So what can a patient do?  A patient looking for information in this area can try a couple of things.  First of all, they can read the studies themselves.  Many of the abstracts and papers are available on various websites (such as pubmed.gov).  Looking at the studies themselves (especially the ones not sponsored by industry), one will readily see that there is a consistent and clear signal with the use of these antidepressant medications and pregnancy complications.  The second thing they can do is to seek out and listen to the experts who are not funded by the drug companies.  There are experts out there who do not take money from the drug industry and just want to provide clear and accurate information to patients and the public.This area can be complicated, but my message on it is simple 1) the studies being done in the area of antidepressants and pregnancy are very concerning because they show a consistent association between antidepressant use and numerous pregnancy complications and possible long-term neurobehavioral effects.  2) Evidence showing that these drugs are providing benefit to pregnant women and their babies is lacking.  3) Pregnant women and the public should be aware of this information.